Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

AIM: To explore the correlation between the integrity of the macular microstructures and the visual outcomes before and after idiopathic macular epiretinal membrane(IMEM)surgery.METHODS: A total of 43 patients(43 eyes)with IMEM who were treated in our hospital between January 2017 and December 2019 were selected. The best corrected visual acuity(BCVA)of each patient was examined preoperatively and at 3, 6, 9mo after surgery. Moreover, metamorphopsia(M-chart)examination was given, and spectral domain-optical coherence tomography(SD-OCT)was used to measure central foveal thickness(CFT), subfoveal choroidal thickness(SFCT), the thickness of ganglion cells-inner plexiform layer(GC-IPL)and the length of interdigitation zone(IZ)defect.RESULTS: The BCVA and the metamorphopsia were gradually improved at postoperative 3, 6 and 9 mo(all P<0.05). Moreover, the BCVA was positively correlated with CFT and the length of the IZ defect(P<0.05), while it was not correlated with SFCT and the thickness of GC-IPL(P>0.05). The metamorphopsia assessment was positively correlated with the CFT at postoperative 3, 6, and 9mo(P<0.05), while it was not correlated with SFCT, the thickness of GC-IPL and the length of IZ defect(P>0.05).CONCLUSIONS: The CFT and the length of IZ defect were significantly correlated with the BCVA after IMEM surgery, which can be used as indicators to predict the recovery of visual function after IMEM surgery.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Background The chronic injury of the hematopoietic system caused by ionizing radiation (IR) is often ignored. The essential cause of this injury is the damage of hematopoietic stem and progenitor cells (HSPCs). Objective To explore the long-term effects of IR at different radiation doses and at different radiation fractions of the same radiation dose on HSPCs in the bone marrow of mice, and to provide a scientific basis for reducing the chronic damage to the hematopoietic system caused by IR. Methods A total of 16 male C57BL/6 mice aged 8-10 weeks were randomly divided into four groups that received different doses or fractions of total body X-ray irradiation, including 1.5 Gy×4 irradiation group (n=5), 3 Gy irradiation group (n=4), 6 Gy irradiation group (n=4), and non-irradiation group (n=3). Two months after irradiation, bone marrow cells from each mouse were collected and counted. The clone forming ability of bone marrow cells was analyzed by cobblestone area-forming cell (CAFC) assay. The proportion of HSPCs was measured by flow cytometry. The cell cycle of HSPCs was assessed by antigen identified by monoclonal antibody Ki 67 (Ki-67) and 7-amino-actinomycin D (7-AAD) double staining. The reactive oxygen species (ROS) levels of HSPCs were estimated with a 2,7-dichlorodihydrofluorescein diacetate (DCFDA) probe. The cellular senescence of HSPCs was evaluated with a 5-dodecanoylaminofluorescein di-β-D-galactopyranoside (C12FDG) probe. The expression of senescence related genes such as P16, P19, P21, and P27 was measured by real-time fluorescence quantitative PCR. Results There was no significant change in the numbers of bone marrow cells 2 months after different doses and fractions of radiation (P>0.05). The clone forming ability of bone marrow cells was significantly decreased after 3 Gy and 6 Gy irradiation when compared to non-irradiated mice (P<0.01). HSPCs responded inconsistently to different doses and fractions of irradiation. Overall, there was no significant change in long-term hematopoietic stem cells (LT-HSCs) proportion after irradiation (P>0.05), the proportions of hematopoietic progenitor cells (HPCs), hematopoietic stem cells (HSCs), short-term hematopoietic stem cells (ST-HSCs), and multipotent progenitors 2 (MPP2) increased after irradiation (P<0.05), and the proportions of LSK, MPP1, MPP3, and MPP4 cells decreased after irradiation (P<0.05); except for HPCs and MPP2, the proportion of HSPCs in G0 phase was decreased (P<0.05). The ROS production in HSPCs was increased significantly after 6 Gy irradiation (P<0.05), while the ROS levels after 3 Gy and 1.5 Gy×4 irradiation were similar to that of the non-radiation group (P>0.05). The cellular senescent proportion of HPCs, LSK, and HSCs increased after irradiation (P<0.05). The expression levels of senescence related genes P16, P19, and P21 in HSCs were significantly increased (P<0.05). Conclusion The responses of HSPCs in bone marrow to IR vary depending on doses and fractions of irradiation. Increased ROS production and cellular senescence may be involved in the damage process of HSPCs under radiation settings.

Aim To investigate the role of calcium-independent phospholipase A2(iPLA2)in calcium regu-lation of intrarenal artery smooth muscle contraction.Methods The method of measuring the tension of isolated arterioles was used to explore the effect of bromoenol lactone(BEL), a specific inhibitor of iPLA2, on the tension of the intrarenal arteries in mice induced by different calcium channels, and the laser confocal calcium measurement technology was used to investigate the effect of BEL on the intracellular calcium influx mediated by arachidonic acid-mediated calcium channels.Results The intrarenal artery concentration dependent contractile response induced by the vasoconstrictors phenylephrine and 5-hydroxy tryptamine was inhibited by BEL(P<0.01).The contraction curve induced by CaCl2 was also inhibited by BEL(P<0.05).In the calcium-free K-H solution incubated with nifedipine, the intrarenal artery vasoconstriction caused by the release of sarcoplasmic reticulum calcium and the calcium influx of the SOC channel induced by CaCl2 was inhibited by BEL(P<0.05).BEL significantly inhibited the external calcium influx mediated by the ARC channel of human aortic smooth muscle cell lines incubated with nifedipine(P<0.01).Conclusions iPLA2 mediates the contractile response of intrarenal arteries by regulating the functions of L-type calcium channels, sarcoplasmic reticulum calcium release, SOC channels and ARC channels.

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines. METHODS: A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19. RESULTS: A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P < 0.001), and/or diarrhea (OR: 2.629, 95% CI: 1.109-6.231, P = 0.028) on admission had a higher risk of severe disease. Moreover, stratification analysis indicated that male patients with diabetes were more likely to have severe COVID-19 (71.4% vs. 28.6%, χ2 = 8.183, P = 0.004). CONCLUSIONS The clinical characteristics of those with severe and nonsevere COVID-19 were significantly different. The elderly, male patients with COVID-19, diabetes, and presenting with cough and/or diarrhea on admission may require close monitoring to prevent deterioration.
Adult ; COVID-19/pathology* ; China/epidemiology* ; Comorbidity ; Cough ; Cross-Sectional Studies ; Diarrhea ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors

OBJECTIVE: To evaluate the clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation. METHODS: A retrospective analysis was performed for the preterm infants with a birth weight less than 1 500 g and a gestational age less than 32 weeks who were treated in the neonatal intensive care unit of 20 hospitals in Jiangsu, China from January 2018 to December 2019. According to the intensity of resuscitation in the delivery room, the infants were divided into three groups:non-tracheal intubation ( RESULTS: Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly lower rates of cesarean section and use of antenatal corticosteroid ( CONCLUSIONS For preterm infants with a birth weight less than 1 500 g, the higher intensity of resuscitation in the delivery room is related to lower rate of antenatal corticosteroid therapy, lower gestational age, and lower birth weight. The infants undergoing tracheal intubation or ECRP in the delivery room have an increased incidence rate of adverse clinical outcomes. This suggests that it is important to improve the quality of perinatal management and delivery room resuscitation to improve the prognosis of the infants.
Birth Weight ; Cesarean Section ; China ; Female ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Pregnancy ; Retrospective Studies

OBJECTIVES: To study the survival rate and the incidence of complications of very preterm infants and the factors influencing the survival rate and the incidence of complications. METHODS: The medical data of the very preterm infants with a gestational age of <32 weeks and who were admitted to the Department of Neonatology in 11 hospitals of Jiangsu Province in China from January 2018 to December 2019 were retrospectively reviewed. Their survival rate and the incidence of serious complications were analyzed. A multivariate logistic regression analysis was used to evaluate the risk factors for death and serious complications in very preterm infants. RESULTS: A total of 2 339 very preterm infants were enrolled, among whom 2 010 (85.93%) survived and 1 507 (64.43%) survived without serious complications. The groups with a gestational age of 22-25 CONCLUSIONS The survival rate is closely associated with gestational age in very preterm infants. A low 1-minute Apgar score (≤3) may increase the risk of death in very preterm infants, while high gestational age, high birth weight, and prenatal use of glucocorticoids are associated with the reduced risk of death. A low 5-minute Apgar score (≤3) and maternal chorioamnionitis may increase the risk of serious complications in these infants, while high gestational age and high birth weight may reduce the risk of serious complications.
Female ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases ; Infant, Very Low Birth Weight ; Pregnancy ; Retrospective Studies ; Survival Rate

BACKGROUND: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China. METHODS: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD. RESULTS: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05). CONCLUSION Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.
Birth Weight ; Bronchopulmonary Dysplasia ; China/epidemiology* ; Delivery Rooms ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Extremely Premature ; Infant, Newborn ; Male ; Pregnancy

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
Aged ; Antibodies, Viral ; COVID-19/therapy* ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; Immunization, Passive ; Recombinant Fusion Proteins ; SARS-CoV-2